Abstract

BACKGROUND. Dietary intake of saturated fat is a likely contributor to nonalcoholic fatty liver disease (NAFLD) and insulin resistance, but the mechanisms that initiate these abnormalities in humans remain unclear. We examined the effects of a single oral saturated fat load on insulin sensitivity, hepatic glucose metabolism, and lipid metabolism in humans. Similarly, initiating mechanisms were examined after an equivalent challenge in mice.

CONCLUSION. Saturated fat ingestion rapidly increases hepatic lipid storage, energy metabolism, and insulin resistance. This is accompanied by regulation of hepatic gene expression and signaling that may contribute to development of NAFLD.

REGISTRATION. ClinicalTrials.gov NCT01736202.

FUNDING. Germany: Ministry of Innovation, Science, and Research North Rhine–Westfalia, German Federal Ministry of Health, Federal Ministry of Education and Research, German Center for Diabetes Research, German Research Foundation, and German Diabetes Association. Portugal: Portuguese Foundation for Science and Technology, FEDER – European Regional Development Fund, Portuguese Foundation for Science and Technology, and Rede Nacional de Ressonância Magnética Nuclear.

Figure 1

CONSORT flow diagram.

Forty-four patients underwent screening, which included a medical history, BMI analyses, and bioimpedance and an oral glucose tolerance tests. Of the 44 participants, 19 did not meet the inclusion criteria, 2 declined to participate, and 2 were excluded for other reasons. Twenty-one participants were allocated to receive the intervention, two of whom did not receive the allocated intervention. An additional 5 volunteers were excluded due to changes in inclusion and exclusion criteria (n = 2), as well as changes in the experimental procedure, which yielded data that could not be compared with subsequently acquired data (n = 3). Ultimately, data from 14 individuals were analyzed, except for hepatic lipid and energy analyses (n = 12) and some hepatic glucose flux measurements (n = 9).